Excessive erythrocytosis compromises the blood–endothelium interface in erythropoietin‐overexpressing mice

Abstract

Elevated systemic hematocrit (Hct) increases cardiovascular risk, such as stroke and myocardial infarction. One possible pathophysiological mechanism could be a disturbance of the blood–endothelium interface. The objective of this study was to examine the effects of an elevated systemic Hct on the thickness of the blood–endothelium interface (‘glycocalyx’, or ‘endothelial surface layer – ESL’) as well as flow resistance. We combined intravital microscopy of a transgenic mouse line (tg6) suffering from excessive erythrocytosis (Hct 0.85), microviscometric analysis of hemodynamics, and an in silico flow simulation model. In tg6 mice the glycocalyx/ESL was nearly abolished (thickness: wild‐type control: 0.52 μm, tg6: 0.13 μm), but was readily restored to normal thickness after systemic hemodilution to normal Hct. However, the corresponding increase in vessel diameter had only minor effects on peripheral flow resistance. This suggests that the pathological effects of elevated Hct may be caused by biological corollaries of a reduced ESL thickness and alterations of the blood–endothelium interface, which could include increased white cell–endothelium interaction and/or increased activation of the coagulation system.